BRCA1-RAD51 homologous DNA repair pathway promotes HIV-1 reverse transcription
HIV-1 infection triggers multiple cellular pathways that modulate viral replication and may promote latency. Central to this process is the reverse transcription of the viral RNA into DNA and its integration into host chromatin, both processes being regulated by the cell. Emerging evidence suggests that homologous recombination (HR) proteins, especially RAD51, may influence both pre- and post-integration stages. In this study, we show that HIV-1 induces the rapid formation of RAD51 nuclear foci in a BRCA1/2-dependent manner, with RAD51 loading onto viral DNA immediately during reverse transcription. Using ChIP, imaging, and biochemical assays, we demonstrate that this process enhances viral infectivity and reverse transcription efficiency. Our findings reveal a previously unidentified cellular response that recruits repair factors to viral DNA, regulating reverse transcription and influencing viral DNA fate. This work uncovers a previously unknown role for RAD51 in modulating early HIV-1 replication, providing insights into host-virus interactions and potential therapeutic strategies.
Authors
- Viviana Scoca (ORCID: https://orcid.org/0000-0003-3791-7499)
- C. Bertinetti
- Marylène Mougel (ORCID: https://orcid.org/0000-0002-0345-1427)
- Olivier Delelis (ORCID: https://orcid.org/0000-0001-9293-2558)
- Francesca Di Nunzio (ORCID: https://orcid.org/0000-0003-2879-3164)
- Vincent Parissi (ORCID: https://orcid.org/0000-0003-1661-7841)
- Paul Lesbats (ORCID: https://orcid.org/0000-0002-4623-0675)
- Fabrice Fleury (ORCID: https://orcid.org/0000-0002-6764-5060)
- Camille Tumiotto (ORCID: https://orcid.org/0000-0001-8547-8107)
- Jacques Dutrieux (ORCID: https://orcid.org/0000-0003-4416-6136)
- Delphine Lapaillerie (ORCID: https://orcid.org/0000-0001-9117-0547)
- Suzanne Figueiredo
- Mathieu Maisch (ORCID: https://orcid.org/0009-0004-1463-3965)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université de Montpellier (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Institut de Recherche en Infectiologie de Montpellier (FR)
- Institut Cochin (FR)
- Unité en Sciences Biologiques et Biotechnologies de Nantes (FR)
- Nantes Université (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2026-07-24
- DOI
- https://doi.org/10.1126/sciadv.aea2430
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales